Multi-center phase 1 safety and efficacy study of nivolumab in renal transplant patients with metastatic malignancy.

Abstract

2567 Background: Organ Transplant Recipients (OTR) are generally excluded from trials of immune checkpoint inhibitors (ICI) due to the reported risk of allograft rejection. A recent systematic review of published case series includes only 65 cases. Transplant organ rejection rates of 41% are reported with cancer response rates of 39%. The majority of OTR treated with ICI have had reduction/cessation of immunosuppression (IS) prior to ICI. Isolated IS reduction is associated with organ rejection and therefore either IS manipulation alone and/or ICI could induce organ rejection episodes. Methods: Renal OTR with incurable cancer, for whom ICI would normally be used in the general population (without an organ transplant), were eligible if creatinine < 180 umol/l, no donor specific HLA antibodies and ECOG < 2. Treatment was with nivolumab (3mg/kg q 14 days for 5 doses, then 480 mg q 28 days), without manipulation of IS and pre-ICI-exposure alloimmune risk assessment. Treatment continued till progression, patient refusal, or graft rejection. Primary endpoint was rate of irretrievable renal graft rejection. Results: 15 patients (9 male:6 female; median age 66.6 years) were enrolled and treated with a median (range) 3(1-42) infusions and with median (range) follow-up of 128 (11-784) days. Tumour types included:1 melanoma; 2 renal tract; 1 hepatocellular carcinoma; 1 Merkel cell; 1 adenocarcinoma lung; 1 MSI high colorectal, 8 squamous cell carcinoma (SCC) head and neck. 2 patients experienced rejection; one at day 28 (2 infusions); one at day 36 (3 infusions). Both had SCC and have had a CR. One is on haemodialysis and alive at 2 years the other a creatinine 450 umol/l. Both rejections treated with steroid, plasma-exchange and anti-thymocyte-globulin (ATG). 1 patient (metastatic bladder cancer) experienced graft loss (at 300 days) due to ureteric-stent bleed and BK-nephritis indirectly related to nivolumab- this patient died of progressive disease at 65 days after nivolumab cessation. Median (range) progression free disease (PD) with ≥ 2 infusions was 300 (68-784+) days. There were 5 CR (1 MSI high colorectal, 4 SCC) median duration of response 13 months and 2 PR (1 SCC 1 bladder)- 1 without PD. Conclusions: In this interim analysis, rejection rates in OTR with incurable cancers treated with ICI was 2/15 (13%) when IS is maintained and there is pre exposure alloimmune assessment. The combined CR and PR rate was 7/15 (47%). Clinical trial information: 12617000741381.